Separation of physiological very low frequency fluctuation from aliasing by switched sampling interval fMRI scans
Introduction
Blood-oxygen-level-dependent (BOLD) T2*-weighted magnetic resonance (MR) images reflect cortical blood flow and oxygenation alterations. The BOLD signal variability is related to either neuronal activation or spontaneous vasomotor waves [1], [2], [3], [4], [5]. The spontaneous BOLD fluctuations have a nonrandom structure and they reflect functional connectivity and default mode brain activity via vasomotor-wave-like temporal BOLD signal fluctuations [3], [5], [6], [7], [8], [9]. The very low frequency fluctuations are so strong in anesthetized child brain cortex that they can be detected as statistically independent BOLD signal sources with independent component analysis [7].
The cerebral blood flow and metabolism of children are markedly enhanced (i.e., up to two times) compared to adults [10], [11]. The elevated baseline blood flow in children may enhance the conduction of the cardiorespiratory pulses inside the cranial vault. The physiological pulsations of CSF induce steady-state free precession (SSFP) disturbances in serial echo-planar imaging (EPI) scans having shorter TR than the T2-relaxation time of CSF (T2CSF). The SSFP disturbances can induce low-frequency signal oscillations in serial EPI image signal [12]. Physiological pulsations that have higher frequencies than critically sampled may, on the other hand, cause aliasing of fluctuation power to lower frequencies [13]. The aliasing problem is present with all conventional fMRI scans that have a long TR [13].
In children, heart pulsation may be over 2 Hz and so the image TR should be smaller than 250 ms if aliasing is to be theoretically avoided (Appendix A). Fast MRI data sampling rates and data filtering can be used to avoid signal aliasing, but then usually TR has to be set low and spatial coverage has to be compromised [13], [14], [15]. When using low TRs, the fluctuations related to disturbance of SSFP are increased and BOLD signal-to-noise ratio (SNR) is reduced [12], [13]. K-space phase data analysis and temporal reordering of images can provide data on physiological fluctuations for estimation of noise aliasing [13], [16]. The temporal reordering procedures have problems with the reordering of frequency harmonics, and spatial analysis regarding the aliased signals is not straightforward [13].
The aim of the study was to show that the VLF BOLD signal fluctuation in the occipital brain cortex of anesthetized children is not aliased noise, but rather a true physiological signal. A simple method that uses relatively high TR values for the detection of aliased signals was used. First of all, the subjects were repetitively imaged with two sampling intervals that were not a direct multiplication of the other. Secondly, the TRs chosen were rather long (i.e., 500 and 1200 ms) in order to decrease the possible physiological pulsation-induced disturbances of SSFP in serial EPI acquisitions [12]. After switching of the sampling rates, a real physiological signal fluctuation will stay in the same frequency, and aliased oscillations will shift along the frequency scale.
Section snippets
Materials and methods
The Ethical Committee of the University of Oulu had approved the study, and informed consent to the imaging was obtained from the parents. The 11 children (mean 4.9±1.4 years, eight male, three female) were imaged in order of admittance for clinical routine brain MR scans. The anesthesiologist sedated the subjects after midazolam premedication (0.3 mg/kg) with intravenous thiopental (5–6 mg/kg) boluses until the subjects slept with spontaneous breathing [5].
The imaging was performed using a
Results
No phantom scans showed any sign of elevated low-frequency fluctuations (Fig. 1). The 40 ICA signal sources of the phantom data showed no signs of signal sources typical of the ones detected in the subjects in spatial or frequency domain. None of the studied subjects presented significant motion (>0.6 mm) artefacts in the center of mass (COM) analysis. In the total image spectrum, the physiological signal-related power peaks are elevated clearly over the noise level typical of phantom data (
Discussion
The prominent BOLD signal sources in the occipital cortices of the anesthetized children associated with spontaneous VLF fluctuations are not aliased artefacts. Nine of 11 subjects showed stable VLF power peaks in the occipital cortex of the two consecutive scans. The VLF fluctuation in these sources originated from real physiological phenomenon rather than from aliased noise. The SSFP fluctuations are present when the TR used is less than the T2 relaxation time of CSF. However, the VLF BOLD
Conclusion
The statistically independent BOLD signal sources presenting very low frequency (VLF) fluctuation in the brain occipital cortex of the anesthetized children are physiological fluctuations and not aliased noise. Arterial BOLD signal sources are affected by aliasing. Switched sampling interval scanning enables the separation of aliased and nonaliased BOLD sources with correctly selected fMRI image sampling rates.
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